Pharmakologische Modulation des "oxidative burst" aktivierter neutrophiler Granulozyten in Anwesenheit von anoxischen Kardiomyozyten

Abstract

Reoxygenation of ischemic myocardium may be harmful due to the formation of free radicals. Therefore, experiments were carried out with a co-incubation ofisolated myocytes and isolated neutrophils from rats. Myocytes were kept for 12h in anoxic conditions. Neutrophils were stimulated with N-formylMet-Leu-Phe (fMLP). The free radical burst (FRB) was detected by a luminol mediated bioluminescence assay. Anoxic myocytes rapidly increase the FRB ofactivated neutrophils to about 844% compared to normoxic myocytes as controls. The FRB can be reduced by addition of superoxid-dismutase (SOD),catalase and gluthation-peroxidase to about 85%, 77% and 72% of the 12h anoxic myocyte group. A further reduction was observed when SOD and catalasetogether were added (93%). Similary, treatment of normoxic myocytes by diethyldithiocarbamate (a SOD inhibitor) increases the burst formation to about200% of the control group. The formation of the FRB in the presence of 12h anoxic myocytes was also decreased by addition of isoproterenol (54%) andverapamil (45%). Adenosine agonists like N6-2-phenylisopropyladenosine, 5`N-ethylcarboxamidoadenosine and cyclopentyl-adenosine can also reduce thefMLP activated neutrophil FRB to about 86%, 77% and 70%, respectively. In conclusion, anoxic myocytes have a better chance of survival in co-culture withactivated neutrophils when substances which reduce the free radical formation by different pathways are added.